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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has emerged as a global pandemic. Seroprevalence surveillance is urgently needed to estimate and monitor the growing burden of coronavirus disease 2019 (COVID-19). The aim of this study is to estimate the seroprevalence of SARS-CoV-2 infection among worker population residing in areas under lockdown in Kuwait and investigated their risk factors associated with a positive status. From April 18 to May 10, 2020 a randomly sampled, worker-based survey was conducted in 7 governorate in Kuwait (Ahmadi, Farwaniya, Hawali, Asma, Jahra, and Mubarak Alkabeer) among 10,256 workers. SARS-CoV-2 IgG and IgM antibodies was assessed using a commercially point-of-care lateral flow immunoassay (Biozek medical COVID-19 IgG/IgM Rapid Test Cassette). We estimated an overall seroprevalence (IgG or IgM positive) of 5.9% (95% CI: 5.4–6.3). Notably, SARS-CoV-2 seropositivity was significantly higher in males (6.2%) than females (1.9%) ( p

The coronavirus disease 2019 (COVID-19) pandemic has rapidly spread to most countries around the world. Disproportionate spread of COVID-19 among the Indian community in Kuwait prompted heightened surveillance in this community.To study the epidemiological characteristics of COVID-19 patients and their contacts among the Indian community in Kuwait.Data collection was done as a part of contact tracing efforts undertaken by the Kuwaiti Ministry of Health.We analysed contact-tracing data for the initial 1348 laboratory-confirmed Indian patients and 6357 contacts (5681 close and 676 casual). The mean (standard deviation) age of the patients was 39.43 (10.5) years and 76.5% of the cases were asymptomatic or had only mild symptoms. Asymptomatic patients were significantly older [40.05 (10.42) years] than patients with severe symptoms [37.54 (10.54) years] (P = 0.024). About 70% of the patients were living in shared accommodation. Most of the close contacts were living in the same household, as compared with casual contacts, who were primarily workplace contacts (P0.001). Among the different occupations, healthcare workers had the highest proportion of cases (18.4%). Among the 216 pairs of cases with a clear relationship between the index and secondary cases, the mean serial interval was estimated to be 3.89 (3.69) days, with a median of 3 and interquartile range of 1-5 days.An early increase in the number of COVID-19 cases among the Indian community could be primarily attributed to crowded living conditions and the high proportion of healthcare workers in this community.الخصائص الوبائية لحالات الإصابة بمرض كوفيد-19 بين الهنود المقيمين في دولة الكويت.جاجان باسكارادوس، عائشة السميط، شاهر مالك، جيتندرا أريجا، أمريتا جيفارجيز، روي فرانسيس، آجاي فازيودان، راجيش ألكسندر، برامود مينون، سحر بهزادي، فاطمة الوهيب، فهد الغملاس، محمد الصيادين، بثينة المظف.انتشرت جائحة مرض فيروس كورونا 2019 (كوفيد-19) بسرعة في معظم بلدان العالم. وأدى الانتشار المفرط لمرض كوفيد-19 بين الجالية الهندية في الكويت إلى زيادة الترصد في هذا المجتمع.هدف هذا البحث الى دراسة الخصائص الوبائية لدى مرضى كوفيد-19 ومُالِطيهم في الجالية الهندية بالكويت.جُِعَت البيانات في إطار جهود تتبُّع المُخالِطين التي قامت بها وزارة الصحة الكويتية.حلَّلنا بيانات تتبُّع المُخالِطين لعدد أولي شمل 1348 مريضًا هنديًا مؤكَّدة إصابتهم مختبريًا و 6357 من المُخالِطين (5681 من المُخالِطين مخالطة مقربة و 676 من المُخالِطين مخالطة عارضة). وبلغ متوسط عمر المرضى (الانحراف المعياري) 39.43 (10.5) عامًا، وكان 76.5٪ من الحالات عديمة الأعراض أو لديهم أعراض خفيفة فقط. وكان المرضى عديمو الأعراض أكبر سنًا بكثير [40.05 (10.42) عامًا] من المرضى الذين يعانون من أعراض وخيمة [37.54 (10.54) عامًا] (الاحتمالية = 0.024). وكان نحو 70٪ من المرضى يعيشون في أماكن إقامة مشتركة. وكان معظم المُخالِطين المقربين يعيشون في المنزل نفسه، مقارنة بالمُخالِطين الذين كانوا على اتصال عارض بالمرضى في محل العمل في المقام الأول (الاحتمالية0.001). ومن بين المهن المختلفة، كانت أعلى نسبة للحالات بين العاملين في مجال الرعاية الصحية (18.4٪). ومن بين 216 زوجًا من الحالات ذات العلاقة الواضحة بين الحالات المرجعية والثانوية، قُدِّر متوسط الفاصل المتسلسل بما يبلغ 3.89 (3.69) يومًا، بمتوسط 3 أيام والمدى الربيعي 1–5 أيام.يمكن أن تعزى الزيادة المبكرة في عدد حالات الإصابة بمرض كوفيد-19 بين الجالية الهندية في المقام الأول إلى الظروف المعيشية المزدحمة والنسبة المرتفعة للعاملين في مجال الرعاية الصحية في هذه الجالية.Caractéristiques épidémiologiques des cas de COVID-19 chez les Indiens résidant au Koweït.La pandémie de maladie à coronavirus 2019 (COVID-19) s’est rapidement propagée vers la plupart des pays du monde. La propagation disproportionnée de la COVID-19 au sein de la communauté indienne du Koweït a incité à une surveillance accrue de cette communauté.Étudier les caractéristiques épidémiologiques des patients atteints de COVID-19 et de leurs contacts au sein de la communauté indienne du Koweït.La collecte des données a été effectuée dans le cadre des efforts de traçage des contacts menés par le ministère de la Santé koweïtien.Nous avons analysé les données relatives à la recherche des contacts pour les 1348 patients indiens initiaux confirmés en laboratoire et les 6357 contacts (5681 contacts rapprochés et 676 occasionnels). L'âge moyen (écart type) des patients était de 39,43 ans (10,5) et 76,5 % des cas étaient asymptomatiques ou ne présentaient que des symptômes légers. Les patients asymptomatiques étaient significativement plus âgés [40,05 ans (10,42)] que les patients présentant des symptômes graves [37,54 ans (10,54)] p = 0,024). Environ 70 % des patients résidaient dans un logement partagé. La plupart des contacts rapprochés vivaient dans le même foyer, alors que les contacts occasionnels étaient principalement des contacts sur le lieu de travail (p0,001). Parmi les différentes professions, les agents de santé présentaient la plus forte proportion de cas (18,4 %). Sur les 216 paires de cas présentant une relation claire entre le cas index et le cas secondaire, l'intervalle sériel moyen a été estimé à 3,89 jours (3,69), avec un intervalle médian de 3 et un intervalle interquartile de 1 à 5 jours.Une augmentation précoce du nombre de cas de COVID-19 au sein de la communauté indienne pourrait être principalement attribuée aux conditions de surpeuplement des logements et à la forte proportion d’agents de santé dans cette communauté.

Background In Kuwait, prior to the first case of COVID-19 being reported in the country, mass screening of incoming travelers from countries with known outbreaks was performed and resulted in the first identified cases in the country. All COVID-19 cases at the time and subsequently after, were transferred to a single center, Jaber Al-Ahmad Al-Sabah Hospital, where the patients received standardized investigations and treatments. The objective of this study was to characterize the demographics, clinical manifestations and outcomes in this unique patient population. Methods This retrospective cohort study was conducted between 24th February 2020 and 20th April 2020. All consecutive patients in the entire State of Kuwait diagnosed with COVID-19 according to WHO guidelines and admitted to Jaber Al-Ahmad Al-Sabah Hospital were recruited. Patients received standardized investigations and treatments. Multivariable analysis was used to determine the associations between risk factors and outcomes. Findings Of 1096 patients, the median age was 41 years and 81% of patients were male. Most patients were asymptomatic on admission (49.5%), 69.4% had no signs of infection and 94.6% were afebrile. Only 3.6% of patients required an ICU admission and 1.7% were dead at the study’s cutoff date. On multivariate analysis, the risk factors found to be significantly associated with admission to intensive care were age above 50 years old, a qSOFA score above 0, smoking, elevated CRP and elevated procalcitonin levels. Asthma, smoking and elevated procalcitonin levels correlated significantly with mortality in our cohort.To our knowledge, this is the first large retrospective cohort study observing the characteristics of the initial consecutive COVID-19 patients of an entire country. Further, large proportion of asymptomatic patients provides novel insights into the clinical features of patients with milder disease. Funding Research Grant Awarded by the Kuwait Foundation for the Advancement of Science.

BackgroundCOVID19 is worldwide pandemic that is mild in the majority of patients but can result in a pneumonia like illness with progression to acute respiratory distress syndrome and death. Predicting the disease severity at time of diagnosis can be helpful in prioritizing hospital admission and resources.MethodsWe prospectively recruited 1096 consecutive patients with COVID19 from the Jaber Hospital, a COVID19 facility in Kuwait, between 24 February and 20 April 2020. The primary endpoint of interest was disease severity defined algorithmically. Predefined risk variables were collected at the time of PCR based diagnosis of the infection. Prognostic model development used 5-fold cross-validated regularized logit regression. The cohort was divided into a training and validation cohort and all model development proceeded on the training cohort.ResultsThere were 643 patients with clinical course data of whom 94 developed severe COVID19. In the final model, age, CRP, procalcitonin, lymphocyte and monocyte percentages and serum albumin were independent predictors of a more severe illness course. The final prognostic model demonstrated good discrimination, calibration and internal validity.ConclusionWe developed and validated a simple score calculated at time of diagnosis that can predict patients with severe COVID19 disease.

Background COVID-19 is a worldwide pandemic that is mild in most patients but can result in a pneumonia like illness with progression to acute respiratory distress syndrome and death. Predicting the disease severity at time of diagnosis can be helpful in prioritizing hospital admission and resources. Methods We prospectively recruited 1096 consecutive patients of whom 643 met the inclusion criterion with COVID-19 from Jaber Hospital, a COVID-19 facility in Kuwait, between 24 February and 20 April 2020. The primary endpoint of interest was disease severity defined algorithmically. Predefined risk variables were collected at the time of PCR based diagnosis of the infection. Prognostic model development used 5-fold cross-validated regularized logit regression. The model was externally validated against data from Wuhan, China. Results There were 643 patients with clinical course data of whom 94 developed severe COVID-19. In the final model, age, CRP, procalcitonin, lymphocyte percentage, monocyte percentages and serum albumin were independent predictors of a more severe illness course. The final prognostic model demonstrated good discrimination, and both discrimination and calibration were confirmed with an external dataset. Conclusion We developed and validated a simple score calculated at time of diagnosis that can predict patients with severe COVID-19 disease reliably and that has been validated externally. The KPI score calculator is now available online at covidkscore.com

Background In Kuwait, prior to the first case of COVID-19 being reported in the country, mass screening of incoming travelers from countries with known outbreaks was performed and resulted in the first identified cases in the country. All COVID-19 cases at the time and subsequently after, were transferred to a single center, Jaber Al-Ahmad Al-Sabah Hospital, where the patients received standardized investigations and treatments. The objective of this study was to characterize the demographics, clinical manifestations, and outcomes in this unique patient population. Methods This retrospective cohort study was conducted between 24th February 2020 and 20th April 2020. All consecutive patients in the entire State of Kuwait diagnosed with COVID-19 according to WHO guidelines and admitted to Jaber Al-Ahmad Al-Sabah Hospital were included. Patients received standardized investigations and treatments. Multivariable analysis was used to determine the associations between risk factors and outcomes (admission to intensive care and/or mortality). Findings Of 1096 patients, the median age was 41 years and 81% of patients were male. Most patients were asymptomatic on admission (46.3%), of whom 35 later developed symptoms, and 59.7% had no signs of infection. Only 3.6% of patients required an ICU admission and 1.7% were dead at the study's cutoff date. On multivariable analysis, the risk factors found to be significantly associated with admission to intensive care were age above 50 years old, a qSOFA score above 0, smoking, elevated CRP and elevated procalcitonin levels. Asthma, smoking and elevated procalcitonin levels correlated significantly with mortality in our cohort.

Background: The frequency of metabolic alkalosis among adults with stable severe CF-lung disease is unknown. Methods: Retrospective chart review. Results: Fourteen CF and 6 COPD (controls) patients were included. FEV1 was similar between the two groups. PaO2 was significantly higher in the COPD (mean ± 2 SD is 72.0 ± 6.8 mmHg,) than in the CF group (56.1 ± 4.1 mmHg). The frequency of metabolic alkalosis in CF patients (12/14, 86%) was significantly greater (p=0.04) than in the COPD group (2/6, 33%). Mixed respiratory acidosis and metabolic alkalosis was evident in 4 CF and 1 COPD patients. Primary metabolic alkalosis was observed in 8 CF and none of the COPD patients. One COPD patient had respiratory and metabolic alkalosis. Conclusions: Metabolic alkalosis is more frequent in stable patients with CF lung disease than in COPD patients. This might be due to defective CFTR function with abnormal electrolyte transport within the kidney and/ or gastrointestinal tract.

Background and objective: Creatine improves muscle strength in exercising healthy individuals, and in patients with neuromuscular disease and heart failure. The aim of this study was to assess whether creatine supplementation improves pulmonary rehabilitation (PR) outcomes in patients with COPD. Methods: A systematic review and meta-analysis was performed of randomized controlled trials published between January 1966 and February 2009 that evaluated the effect of creatine compared with placebo on exercise capacity, muscle strength and health-related quality of life (HR-QoL) in patients undergoing PR for COPD. The pooled estimates were expressed as mean differences (MD) or standardized mean differences (SMD). Results: Four randomized controlled trials that included 151 patients were identified. There was no effect of creatine supplementation on exercise capacity (SMD −0.01, 95% CI: −0.42 to 0.22, n = 151). Creatine supplementation did not improve lower extremity muscle strength (SMD 0.03, 95% CI: −0.55 to 0.61, n = 140) or upper limb muscular strength (SMD 0.02, 95% CI: −0.33 to 0.38, n = 128) compared with placebo. Two studies (n = 48) assessed quality of life using the St. George's Respiratory Disease Questionnaire. There were no differences in HR-QoL according to domain or total scores. Overall, creatine appeared to be safe and was well tolerated. Quality assessment of the studies showed important limitations. Conclusions: Creatine supplementation does not improve exercise capacity, muscle strength or HR-QoL in patients with COPD receiving PR. However, important limitations were identified in the quality of the available evidence, suggesting that further research is required in this area.

Chronic low-grade inflammation and dysregulation of the stress defense system are cardinal features of obesity, a major risk factor for the development of insulin resistance and diabetes. Dual-specificity protein phosphatase 1 (DUSP1), known also as MAP kinase phosphatase 1 (MKP1), is implicated in metabolism and energy expenditure. Mice lacking DUSP1 are resistant to high-fat diet-induced obesity. However, the expression of DUSP1 has not been investigated in human obesity. In the current study, we compared the expression pattern of DUSP1 between lean and obese nondiabetic human subjects using subcutaneous adipose tissue (SAT) and peripheral blood mononuclear cells (PBMCs). The levels of DUSP1 mRNA and protein were significantly increased in obese subjects with concomitant decrease in the phosphorylation of p38 MAPK (p-p38 MAPK) and PGC-1α and an increase in the levels of phospho-JNK (p-JNK) and phospho-ERK (p-ERK). Moreover, obese subjects had higher levels of circulating DUSP1 protein that correlated positively with various obesity indicators, triglycerides, glucagon, insulin, leptin, and PAI-1 ( P < 0.05) but negatively with V̇o2max and high-density lipoprotein ( P < 0.05). The observation that DUSP1 was overexpressed in obese subjects prompted us to investigate whether physical exercise could reduce its expression. In this study, we report for the first time that physical exercise significantly attenuated the expression of DUSP1 in both the SAT and PBMCs, with a parallel increase in the expression of PGC-1α and a reduction in the levels of p-JNK and p-ERK along with attenuated inflammatory response. Collectively, our data suggest that DUSP1 upregulation is strongly linked to adiposity and that physical exercise modulates its expression. This gives further evidence that exercise might be useful as a strategy for managing obesity and preventing its associated complications.

Non-steroidal anti-inflammatory drugs are used daily by millions of patients worldwide for the management of various inflammatory diseases. Many well-documented adverse reactions are related to the use of these drugs. We report a fifty-four year-old woman with anaphylaxis after ingestion of ibuprofen liquid in a gelatin capsule. Eventually this was concluded to have resulted from hypersensitivity to the gelatin component of the capsule, which was likely IgE-mediated because of the positive skin test to gelatin. Gelatin allergy is only relevant for patients ingesting specific capsule formulation. The allergist/clinical immunologist must keep in mind the possibility of gelatin allergy.

Objective: Recent studies have demonstrated a protective role for IL-33 against obesity-associated inflammation, atherosclerosis and metabolic abnormalities. IL-33 promotes the production of T helper type 2 (Th2) cytokines, polarizes macrophages towards a protective alternatively activated phenotype, reduces lipid storage and decreases the expression of genes associated with lipid metabolism and adipogenesis. Our objective was to determine the level of serum IL-33 in non-diabetic and diabetic subjects, and to correlate these levels with clinical (BMI and body weight) and metabolic (serum lipids and HbA1c) parameters. Methods: The level of IL-33 was measured in the serum of lean, overweight and obese non-diabetic and diabetic subjects, and then correlated with clinical and metabolic parameters. Results: Non-lean subjects had significantly (P = 0.01) lower levels of IL-33 compared to lean controls. IL-33 was negatively correlated with the BMI and body weight in lean and overweight, but not obese (non-diabetic and diabetic), subjects. IL-33 is associated with protective lipid profiles, and is negatively correlated with HbA1c, in non-diabetic (lean, overweight and obese) but not diabetic subjects. Conclusions: Our data support previous findings showing a protective role for IL-33 against adiposity and atherosclerosis, and further suggest that reduced levels of IL-33 may put certain individuals at increased risk of developing atherosclerosis and insulin resistance. Therefore, IL-33 may serve as a novel marker to predict those who may be at increased risk of developing atherosclerosis.

Chronic low-grade inflammation and uncontrolled metabolic stress response are cardinal features of obesity; a major risk factor for the development diabetes. Dual specificity protein phosphatase 1 (DUSP1) is implicated in metabolism and energy expenditure. Mice lacking DUSP1 are resistant to high fat diet-induced obesity. However, the expression of DUSP1 has not been investigated in human obesity. In the current study, we compared the expression pattern of DUSP1 between lean and obese non-diabetic human subjects using subcutaneous adipose tissue and peripheral blood mononuclear cells. The levels of DUSP1 mRNA and protein were significantly increased in obese subjects with concomitant decrease in the phosphorylation of p38 MAPK and PGC-1α and an increase in the levels of phospho-JNK and phospho-ERK. Moreover, obese subjects had higher levels of circulating DUSP1 protein that correlated positively with various obesity indicators, triglycerides, glucagon, insulin, leptin and PAI-1 (P

Sedentary lifestyle and excessive energy intake are prominent contributors to obesity; a major risk factors for the development of insulin resistance, type 2 diabetes and cardiovascular diseases. Elucidating the molecular mechanisms underlying these chronic conditions is of relevant importance as it might lead to the identification of novel anti-obesity targets. The purpose of the current study is to investigate differentially expressed proteins between lean and obese subjects through a shot-gun quantitative proteomics approach using peripheral blood mononuclear cells (PBMCs) extracts as well as potential modulation of those proteins by physical exercise. Using this approach, a total of 47 proteins showed at least 1.5 fold change between lean and obese subjects. In obese, the proteomic profiling before and after 3 months of physical exercise showed differential expression of 38 proteins. Thrombospondin 1 (TSP1) was among the proteins that were upregulated in obese subjects and then decreased by physical exercise. Conversely, the histone deacetylase 4 (HDAC4) was downregulated in obese subjects and then induced by physical exercise. The proteomic data was further validated by qRT-PCR, Western blot and immunohistochemistry in both PBMCs and adipose tissue. We also showed that HDAC4 levels correlated positively with maximum oxygen consumption (VO2 Max) but negatively with body mass index, percent body fat, and the inflammatory chemokine RANTES. In functional assays, our data indicated that ectopic expression of HDAC4 significantly impaired TNF-α-dependent activation of NF-κB, establishing thus a link between HDAC4 and regulation of the immune system. Together, the expression pattern of HDAC4 in obese subjects before and after physical exercise, its correlation with various physical, clinical and metabolic parameters along with its inhibitory effect on NF-κB are suggestive of a protective role of HDAC4 against obesity. HDAC4 could therefore represent a potential therapeutic target for the control and management of obesity and presumably insulin resistance.

Background/Objective Osteopontin (OPN) and IL-18 are known inflammatory mediators and both participate in a wide range of biological processes linked to immunological disorders. Since an interaction between OPN and IL-18 has not been studied in obesity, we investigated whether: (i) their levels were simultaneously elevated in obese individuals; (ii) OPN was associated with IL-18 in obese individuals and (iii) their levels associated with fasting blood glucose (FBG) and BMI. Subjects and Methods PBMCs and plasma samples were isolated from 60 individuals including lean as well as overweight and obese individuals. Subcutaneous adipose tissue samples were obtained. OPN and IL-18 were measured by ELISA. OPN and IL-18 mRNA expression was quantified by real time quantitative RT-PCR. Results Obese individuals exhibited significantly increased circulating OPN levels as compared with lean individuals (obese 2865±101; lean 1681±116 pg/ml; P

The first case of cavitary pulmonary disease caused by Purpureocillium lilacinum is described. The isolate showed atypical microscopic characteristics similar to Acremonium and Fusarium spp., which necessitated molecular identification by sequencing of multiple conserved loci. The patient responded to voriconazole, reinforcing its therapeutic efficacy for P. lilacinum infections.

Objective: To develop an Arabic version of the Chronic Respiratory Disease Questionnaire (CRQ) to be known as ArabiCRQ. Materials and Methods: We conducted a linguistic validation of the CRQ in the Arabic language. The validation process involved 4 phases, including forward and backward translations, pilot testing, and revision to produce a final version of the ArabiCRQ. Five native Arabic-speaking patients with chronic obstructive pulmonary disease completed the ArabiCRQ both in initial and follow-up visits. Wording was modified according to feedback the participants provided. Results: Two of the patients’ scores changed appreciably, despite ensuring their clinical stability. Conclusion: The ArabiCRQ may be a valuable tool to assess the health-related quality of life in patients with chronic respiratory diseases.

BACKGROUND: Some patients with chronic obstructive pulmonary disease (COPD) may benefit from oral steroid therapy. These steroid-responsive patients are diagnosed based on laboratory spirometry. We hypothesize that daily, home-based spirometry is a better tool. METHODS: Thirty patients with COPD underwent a single-blinded study, with a crossover design. They received 2 weeks of placebo followed by 2 weeks of prednisone therapy (40 mg/day). Laboratory spirometry was done at the beginning and end of the study and daily home-based spirometry was done twice a day. RESULTS: Analysis of variance model was used. The variability of the median day-to-day forced expiratory volume in 1 s (FEV1) was 72.5 mL (25th percentile of 40 mL and 75th percentile of 130 mL). The daily FEV1 variation was 70 mL (25th percentile of 50 mL and 75th percentile of 100 mL). The overall laboratory FEV1 variability was larger after the steroid course (P < 0.001), but not clinically significant. The variability was not significant postplacebo treatment compared with the baseline values. For home-based spirometry, steroid treatment was not significantly different. The majority (97%) completed more than 80% of the measurements. Ninety percent of the performed tests were considered acceptable. Only 53% of the tests were considered accurate. Overall both laboratory and home-based measurements did not show significant association between airway responsiveness and dyspnea or exercise capacity. CONCLUSION: Twice-daily home measurements of FEV1 might be better than the conventional approach to identify steroid responsive COPD patients. However, this finding was only statistically but not clinically significant. Therefore, we would not recommend this approach to identify COPD patients with steroid responsiveness.

Background Obesity is characterized by a chronic low-grade inflammation and altered stress responses in key metabolic tissues. Impairment of heat shock response (HSR) has been already linked to diabetes and insulin resistance as reflected by decrease in heat shock proteins (HSPs) expression. However, the status of HSR in non-diabetic human obese has not yet been elucidated. The aim of the current study was to investigate whether obesity triggers a change in the HSR pattern and the impact of physical exercise on this pattern at protein and mRNA levels. Methods Two groups of adult non-diabetic human subjects consisting of lean and obese (n = 47 for each group) were enrolled in this study. The expression pattern of HSP-27, DNAJB3/HSP-40, HSP-60, HSC-70, HSP72, HSP-90 and GRP-94 in the adipose tissue was primarily investigated by immunohistochemistry and then complemented by western blot and qRT-PCR in Peripheral blood mononuclear cells (PBMCs). HSPs expression levels were correlated with various physical, clinical and biochemical parameters. We have also explored the effect of a 3-month moderate physical exercise on the HSPs expression pattern in obese subjects. Results Obese subjects displayed increased expression of HSP-60, HSC-70, HSP-72, HSP-90 and GRP-94 and lower expression of DNAJB3/HSP-40 (P

Obesity is a major risk factor for a myriad of disorders such as insulin resistance and diabetes. The mechanisms underlying these chronic conditions are complex but low grade inflammation and alteration of the endogenous stress defense system are well established. Previous studies indicated that impairment of HSP-25 and HSP-72 was linked to obesity, insulin resistance and diabetes in humans and animals while their induction was associated with improved clinical outcomes. In an attempt to identify additional components of the heat shock response that may be dysregulated by obesity, we used the RT(2)-Profiler PCR heat shock array, complemented with RT-PCR and validated by Western blot and immunohistochemistry. Using adipose tissue biopsies and PBMC of non-diabetic lean and obese subjects, we report the downregulation of DNAJB3 cochaperone mRNA and protein in obese that negatively correlated with percent body fat (P = 0.0001), triglycerides (P = 0.035) and the inflammatory chemokines IP-10 and RANTES (P = 0.036 and P = 0.02, respectively). DNAJB positively correlated with maximum oxygen consumption (P = 0.031). Based on the beneficial effect of physical exercise, we investigated its possible impact on DNAJB3 expression and indeed, we found that exercise restored the expression of DNAJB3 in obese subjects with a concomitant decrease of phosphorylated JNK. Using cell lines, DNAJB3 protein was reduced following treatment with palmitate and tunicamycin which is suggestive of the link between the expression of DNAJB3 and the activation of the endoplasmic reticulum stress. DNAJB3 was also shown to coimmunoprecipiate with JNK and IKKβ stress kinases along with HSP-72 and thus, suggesting its potential role in modulating their activities. Taken together, these data suggest that DNAJB3 can potentially play a protective role against obesity.

Introduction Obesity is characterized by a chronic-low grade inflammation and aberrant regulation of various forms of stress response in key metabolic sites. The white adipose tissue has been identified as the predominant site of obesity-associated inflammatory reactions, which are triggered as a consequence of immune cells infiltration. Physical exercise has been widely recognized for treating obesity and metabolic syndromes. The objectives of this study are: (1) To investigate the release pattern of pro- and anti-inflammatory mediators in obese participants, (2) To evaluate the effect of a defined exercise protocol on their release into the circulation, (3) To correlate their expression with the metabolic and stress markers. Methods A total of 600 healthy individuals divided into 3 groups using the body mass index as a reference (lean, overweight and obese) are being enrolled in a 6-month defined exercise protocol. Blood samples and abdominal subcutaneous adipose biopsies are collected at baseline (t0) and after 3 (t3) and 6 (t6) months of exercise. Plasma cytokine and metabolic markers levels were assessed simultaneously using the xMAP multiplex immunobead assay technology (Bioplex). Markers of the oxidative stress, namely ROS and TBARS were measured on plasma or serum using commercially available kits. Gene expression profile was done by RT-PCR using RT-profiler- array kits consisting of the heat shock protein panel, obesity panel and the oxidative stress panel. Western blotting and immunohistochemistry techniques were used to validate the gene expression data. Statistical analyses were performed using SAS software. Results The analysis carried out on a first set of samples indicated significant release of RANTES in obese individuals compared to lean participants ( P Conclusion Our result demonstrated a differential expression of RANTES chemokine in obese participants in comparison to lean control and highlighted its roles in obesity. Exercise was able to restore the normal expression of RANTES. The existence of a negative correlation between RANTES expression and the metabolic and stress responses is suggestive of a pathological role of RANTES and may be considered a potential therapeutic target.

Background Expression profile of the toll like receptors (TLRs) on PBMCs is central to the regulation of proinflammatory markers. An imbalance in the TLRs expression may lead to several types of inflammatory disorders. Furthermore, the dynamic regulation of inflammatory activity and associated impaired production of cytokines by peripheral blood mononuclear cells (PBMCs) in obese individulas remain poorly understood. Therefore, we determined the perturbation in TLRs (TLR2 and TLR4), their adaptor proteins (MyD88, IRAK1 and TRAF6) expression in PBMCs/subcutaneous adipose tissue (AT) as well as inflammatory cytokines changes in obese individuals. Methods mRNA expression levels of TLR2, TLR4, IL-6, TNF-α and adaptor proteins were determined by RT-PCR. TLR2, TLR4 and adaptor proteins expression in AT was determined by immunohistochemistry. Results Obese and overweight individuals showed significantly increased expression of TLR2, TLR4 and MyD88 in both PBMCs and AT as compared with lean individuals (P Conclusions TLRs and adapter proteins were overexpressed in PBMCs from obese subjects, which correlated with increased expression of TNF-α and IL-6. This association may explain a potential pathophysiological link between obesity and inflammation leading to insulin resistance.

Association of obesity with down-regulation of heat shock protein 40 expression and evidence that exercise retrieves its normal expression Jehad Abubakr, Mohamed Abu-Farha, Monira Al-Arouj, Fahad Al-Ghimlas, Irina Al-Khairi, Dalal Al-Mudhaf, Engin Baturcam, Abdullah Bennakhi, Preethi Cherian, Maha Hammad, Jeena John, Sina Kavalakatt, Abdelkrim Khadir, Ali Tiss, Samia Warsame, Said Dermime, Mohammed Dehbi